The risk of all-cause and cause-specific mortality in people prescribed mirtazapine: an active comparator cohort study using electronic health records.

BACKGROUND: Studies have reported an increased risk of mortality among people prescribed mirtazapine compared to other antidepressants. The study aimed to compare all-cause and cause-specific mortality between adults prescribed mirtazapine or other second-line antidepressants. METHODS: This cohort study used English primary care electronic medical records, hospital admission records, and mortality data from the Clinical Practice Research Datalink (CPRD), for the period 01 January 2005 to 30 November 2018. It included people aged 18-99 years with depression first prescribed a selective serotonin reuptake inhibitor (SSRI) and then prescribed mirtazapine (5081), a different SSRI (15,032), amitriptyline (3905), or venlafaxine (1580). Follow-up was from starting to stopping the second antidepressant, with a 6-month wash-out window, censoring at the end of CPRD follow-up or 30 November 2018. Age-sex standardised rates of all-cause mortality and death due to circulatory system disease, cancer, or respiratory system disease were calculated. Survival analyses were performed, accounting for baseline characteristics using inverse probability of treatment weighting. RESULTS: The cohort contained 25,598 people (median age 41 years). The mirtazapine group had the highest standardised mortality rate, with an additional 7.8 (95% confidence interval (CI) 5.9-9.7) deaths/1000 person-years compared to the SSRI group. Within 2 years of follow-up, the risk of all-cause mortality was statistically significantly higher in the mirtazapine group than in the SSRI group (weighted hazard ratio (HR) 1.62, 95% CI 1.28-2.06). No significant difference was found between the mirtazapine group and the amitriptyline (HR 1.18, 95% CI 0.85-1.63) or venlafaxine (HR 1.11, 95% CI 0.60-2.05) groups. After 2 years, the risk was significantly higher in the mirtazapine group compared to the SSRI (HR 1.51, 95% CI 1.04-2.19), amitriptyline (HR 2.59, 95% CI 1.38-4.86), and venlafaxine (HR 2.35, 95% CI 1.02-5.44) groups. The risks of death due to cancer (HR 1.74, 95% CI 1.06-2.85) and respiratory system disease (HR 1.72, 95% CI 1.07-2.77) were significantly higher in the mirtazapine than in the SSRI group. CONCLUSIONS: Mortality was higher in people prescribed mirtazapine than people prescribed a second SSRI, possibly reflecting residual differences in other risk factors between the groups. Identifying these potential health risks when prescribing mirtazapine may help reduce the risk of mortality.

Association between opioid-related deaths and persistent opioid prescribing in primary care in England: A nested case-control study.

AIM: This study aimed to evaluate the association between opioid-related deaths and persistent opioid utilisation in the United Kingdom (UK). METHODS: This nested case-control study used the UK Clinical Practice Research Datalink, linking the Office for National Statistics death registration. Adult opioid users with recorded opioid-related death between 2000 and 2015 were included and matched to four opioid users (controls) based on a disease risk score. Persistent opioid utilisation (opioid prescriptions ≥3 quarters/year and oral morphine equivalent dose ≥4500 mg/year) and psychotropic prescriptions were identified annually during the three patient-years before the date of opioid-related death. Conditional logistic regression was used to assess the association between persistent opioid utilisation and opioid-related death, and the results were reported as adjusted odds ratios (aOR) and 95% confidence intervals (95% CI). RESULTS: Of the 902 149 opioid users, 230 opioid-related deaths (cases) and 920 controls were identified. Persistent opioid utilisation was significantly associated with an increased risk of opioid-related deaths (aOR 1.9, 95% CI 1.2, 2.9) when persistent opioid utilisation was defined by both annual dose and number of quarters. Concurrent prescription of opioids and tricyclic antidepressants (aOR 2.0, 95% CI 1.2, 3.5) or higher dose of benzodiazepine (aOR 6.5, 95% CI 4.0, 10.4) or gabapentinoids (aOR 6.2, 95% CI 2.9, 13.5) were associated with opioid-related death. CONCLUSION: Persistent opioid prescribing and concurrent prescribing of psychotropics were associated with a higher risk of opioid-related death and should be avoided in clinical practice. An evidence-based indicator to monitor the safety of prescribed opioids during opioid deprescribing is needed.

Multi-Objective Routing Optimization for 6G Communication Networks Using a Quantum Approximate Optimization Algorithm.

Sixth-generation wireless (6G) technology has been focused on in the wireless research community. Global coverage, massive spectrum usage, complex new applications, and strong security are among the new paradigms introduced by 6G. However, realizing such features may require computation capabilities transcending those of present (classical) computers. Large technology companies are already exploring quantum computers, which could be adopted as potential technological enablers for 6G. This is a promising avenue to explore because quantum computers exploit the properties of quantum states to perform certain computations significantly faster than classical computers. This paper focuses on routing optimization in wireless mesh networks using quantum computers, explicitly applying the quantum approximate optimization algorithm (QAOA). Single-objective and multi-objective examples are presented as robust candidates for the application of quantum machine learning. Moreover, a discussion about quantum supremacy estimation for this problem is provided.

Incidence and prevalence of primary care antidepressant prescribing in children and young people in England, 1998-2017: A population-based cohort study.

BACKGROUND: The use of antidepressants in children and adolescents remains controversial. We examined trends over time and variation in antidepressant prescribing in children and young people in England and whether the drugs prescribed reflected UK licensing and guidelines. METHODS AND FINDINGS: QResearch is a primary care database containing anonymised healthcare records of over 32 million patients from more than 1,500 general practices across the UK. All eligible children and young people aged 5-17 years in 1998-2017 from QResearch were included. Incidence and prevalence rates of antidepressant prescriptions in each year were calculated overall, for 4 antidepressant classes (selective serotonin reuptake inhibitors [SSRIs], tricyclic and related antidepressants [TCAs], serotonin and norepinephrine reuptake inhibitors [SNRIs], and other antidepressants), and for individual drugs. Adjusted trends over time and differences by social deprivation, region, and ethnicity were examined using Poisson regression, taking clustering within general practitioner (GP) practices into account using multilevel modelling. Of the 4.3 million children and young people in the cohort, 49,434 (1.1%) were prescribed antidepressants for the first time during 20 million years of follow-up. Males made up 52.0% of the cohorts, but only 34.1% of those who were first prescribed an antidepressant in the study period. The largest proportion of the cohort was from London (24.4%), and whilst ethnicity information was missing for 39.5% of the cohort, of those with known ethnicity, 75.3% were White. Overall, SSRIs (62.6%) were the most commonly prescribed first antidepressant, followed by TCAs (35.7%). Incident antidepressant prescribing decreased in 5- to 11-year-olds from a peak of 0.9 in females and 1.6 in males in 1999 to less than 0.2 per 1,000 for both sexes in 2017, but incidence rates more than doubled in 12- to 17-year-olds between 2005 and 2017 to 9.7 (females) and 4.2 (males) per 1,000 person-years. The lowest prescription incidence rates were in London, and the highest were in the South East of England (excluding London) for all sex and age groups. Those living in more deprived areas were more likely to be prescribed antidepressants after adjusting for region. The strongest trend was seen in 12- to 17-year-old females (adjusted incidence rate ratio [aIRR] 1.12, 95% confidence interval [95% CI] 1.11-1.13, p < 0.001, per deprivation quintile increase). Prescribing rates were highest in White and lowest in Black adolescents (aIRR 0.32, 95% CI 0.29-0.36, p < 0.001 [females]; aIRR 0.32, 95% CI 0.27-0.38, p < 0.001 [males]). The 5 most commonly prescribed antidepressants were either licensed in the UK for use in children and young people (CYP) or included in national guidelines. Limitations of the study are that, because we did not have access to secondary care prescribing information, we may be underestimating the prevalence and misidentifying the first antidepressant prescription. We could not assess whether antidepressants were dispensed or taken. CONCLUSIONS: Our analysis provides evidence of a continuing rise of antidepressant prescribing in adolescents aged 12-17 years since 2005, driven by SSRI prescriptions, but a decrease in children aged 5-11 years. The variation in prescribing by deprivation, region, and ethnicity could represent inequities. Future research should examine whether prescribing trends and variation are due to true differences in need and risk factors, access to diagnosis or treatment, prescribing behaviour, or young people's help-seeking behaviour.

Secondary care specialist visits made by children and young people prescribed antidepressants in primary care: a descriptive study using the QResearch database.

BACKGROUND: Antidepressants may be used to manage a number of conditions in children and young people including depression, anxiety, and obsessive-compulsive disorder. UK guidelines for the treatment of depression in children and young people recommend that antidepressants should only be initiated following assessment and diagnosis by a child and adolescent psychiatrist. The aim of this study was to summarise visits to mental health specialists and indications recorded around the time of antidepressant initiation in children and young people in UK primary care. METHODS: The study used linked English primary care electronic health records and Hospital Episode Statistics secondary care data. The study included 5-17-year-olds first prescribed antidepressants between January 2006 and December 2017. Records of visits to paediatric or psychiatric specialists and potential indications (from a pre-specified list) were extracted. Events were counted if recorded less than 12 months before or 6 months after the first antidepressant prescription. Results were stratified by first antidepressant type (all, selective serotonin reuptake inhibitors (SSRIs), tricyclic and related antidepressants) and by age group (5-11 years, 12-17 years). RESULTS: In total, 33,031 5-17-year-olds were included. Of these, 12,149 (37%) had a record of visiting a paediatrician or a psychiatric specialist in the specified time window. The majority of recorded visits (7154, 22%) were to paediatricians. Of those prescribed SSRIs, 5463/22,130 (25%) had a record of visiting a child and adolescent psychiatrist. Overall, 17,972 (54%) patients had a record of at least one of the pre-specified indications. Depression was the most frequently recorded indication (12,501, 38%), followed by anxiety (4155, 13%). CONCLUSIONS: The results suggest many children and young people are being prescribed antidepressants without the recommended involvement of a relevant specialist. These findings may justify both greater training for GPs in child and adolescent mental health and greater access to specialist care and non-pharmacological treatments. Further research is needed to explore factors that influence how and why GPs prescribe antidepressants to children and young people and the real-world practice barriers to adherence to clinical guidelines.

A 15-year overview of increasing tramadol utilisation and associated mortality and the impact of tramadol classification in the United Kingdom.

PURPOSE: This study aimed to develop hypotheses to explain the increasing tramadol utilisation, evaluate the impact of tramadol classification, and explore the trend between tramadol utilisation and related deaths in the United Kingdom. METHODS: This cross-sectional study used individual patient data, the Clinical Practice Research Datalink from 1993 to 2015, to calculate monthly defined daily dose (DDD)/1000 registrants, monthly prevalence and incidence of tramadol users, annual supply days, and mean daily dose of tramadol. Aggregated-level national statistics and reimbursement data from 2004 to 2015 were also used to quantify annual and monthly tramadol DDD/1000 inhabitants and rate of tramadol-related deaths in England and Wales. Interrupted time-series analysis was used to evaluate the impact of tramadol classification in June 2014. RESULTS: Prevalence of tramadol users increased from 23 to 97.6/10 000 registrants from 2000 to 2015. Both annual dose and annual supply days of existing tramadol users were higher than new users. Level and trend of monthly utilisation (ß2 : -12.9, ß3 : -1.6) and prevalence of tramadol users (ß2 : -6.4, ß3 : -0.37) significantly reduced after classification. Both annual tramadol utilisation and rate of tramadol-related deaths increased before tramadol classification and decreased thereafter. CONCLUSIONS: Increasing tramadol utilisation was influenced by the increase in prevalence and incidence of tramadol users, mean daily dose, and day of supply. Prevalence of tramadol users, tramadol utilisation, and reported deaths declined after tramadol classification. Future studies need to evaluate the influencing factors to ensure the safety of long-term tramadol use.

Interventions for preventing high altitude illness: Part 1. Commonly-used classes of drugs.

BACKGROUND: High altitude illness (HAI) is a term used to describe a group of cerebral and pulmonary syndromes that can occur during travel to elevations above 2500 metres (8202 feet). Acute hypoxia, acute mountain sickness (AMS), high altitude cerebral oedema (HACE) and high altitude pulmonary oedema (HAPE) are reported as potential medical problems associated with high altitude. In this review, the first in a series of three about preventive strategies for HAI, we assess the effectiveness of six of the most recommended classes of pharmacological interventions. OBJECTIVES: To assess the clinical effectiveness and adverse events of commonly-used pharmacological interventions for preventing acute HAI. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (OVID), Embase (OVID), LILACS and trial registries in January 2017. We adapted the MEDLINE strategy for searching the other databases. We used a combination of thesaurus-based and free-text terms to search. SELECTION CRITERIA: We included randomized-controlled and cross-over trials conducted in any setting where commonly-used classes of drugs were used to prevent acute HAI. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as expected by Cochrane. MAIN RESULTS: We included 64 studies (78 references) and 4547 participants in this review, and classified 12 additional studies as ongoing. A further 12 studies await classification, as we were unable to obtain the full texts. Most of the studies were conducted in high altitude mountain areas, while the rest used low pressure (hypobaric) chambers to simulate altitude exposure. Twenty-four trials provided the intervention between three and five days prior to the ascent, and 23 trials, between one and two days beforehand. Most of the included studies reached a final altitude of between 4001 and 5000 metres above sea level. Risks of bias were unclear for several domains, and a considerable number of studies did not report adverse events of the evaluated interventions. We found 26 comparisons, 15 of them comparing commonly-used drugs versus placebo. We report results for the three most important comparisons: Acetazolamide versus placebo (28 parallel studies; 2345 participants)The risk of AMS was reduced with acetazolamide (risk ratio (RR) 0.47, 95% confidence interval (CI) 0.39 to 0.56; I2 = 0%; 16 studies; 2301 participants; moderate quality of evidence). No events of HAPE were reported and only one event of HACE (RR 0.32, 95% CI 0.01 to 7.48; 6 parallel studies; 1126 participants; moderate quality of evidence). Few studies reported side effects for this comparison, and they showed an increase in the risk of paraesthesia with the intake of acetazolamide (RR 5.53, 95% CI 2.81 to 10.88, I2 = 60%; 5 studies, 789 participants; low quality of evidence). Budenoside versus placebo (2 parallel studies; 132 participants)Data on budenoside showed a reduction in the incidence of AMS compared with placebo (RR 0.37, 95% CI 0.23 to 0.61; I2 = 0%; 2 studies, 132 participants; low quality of evidence). Studies included did not report events of HAPE or HACE, and they did not find side effects (low quality of evidence). Dexamethasone versus placebo (7 parallel studies; 205 participants)For dexamethasone, the data did not show benefits at any dosage (RR 0.60, 95% CI 0.36 to 1.00; I2 = 39%; 4 trials, 176 participants; low quality of evidence). Included studies did not report events of HAPE or HACE, and we rated the evidence about adverse events as of very low quality. AUTHORS' CONCLUSIONS: Our assessment of the most commonly-used pharmacological interventions suggests that acetazolamide is an effective pharmacological agent to prevent acute HAI in dosages of 250 to 750 mg/day. This information is based on evidence of moderate quality. Acetazolamide is associated with an increased risk of paraesthesia, although there are few reports about other adverse events from the available evidence. The clinical benefits and harms of other pharmacological interventions such as ibuprofen, budenoside and dexamethasone are unclear. Large multicentre studies are needed for most of the pharmacological agents evaluated in this review, to evaluate their effectiveness and safety.

Gravity-assisted valve (GAV) systems to prevent low-pressure headaches in patients with lumboperitoneal shunts.

OBJECTIVES: Low-pressure symptoms after lumboperitoneal (LP) shunting for idiopathic intracranial hypertension (IIH) remain a significant problem. Gravity-assisted valves (GAV) operate at a higher pressure in a vertical position and therefore aim to reduce postural over-drainage. We audited patients with GAV valves inserted in their shunt system to assess their efficacy in reducing low-pressure symptoms and ascertain whether the additional cost of such device can be justified. METHOD: Using a standard proforma, we reviewed patient medical notes and recorded indications and post-operative outcomes in symptom control. RESULTS: In total, 24 patients had the GAV system inserted, 12 had low-pressure symptoms after LP and had LP shunts inserted with GAV valves and 11 in developed low-pressure symptoms after insertion of plane LP shunts and had GAV valves added as secondary procedures. One patient was excluded from the study because the indication for the GAV system was secondary to the presence of low lying cerebellar tonsils (secondary Chiari) rather than headache in a patient with IIH who had undergone previous LP shunt insertion. The GAV system was introduced to prevent further tonsillar decent.Out of 23 patients, 17 patients who had the system inserted to prevent or improve low-pressure symptoms reported improvement in their symptoms. CONCLUSIONS: GAV inserted into LP shunts were effective in reducing low-pressure headaches induced by changes in posture whilst still sufficiently lowering ICP to ameliorate high-pressure symptoms.

Sun protection for preventing basal cell and squamous cell skin cancers.

BACKGROUND: 'Keratinocyte cancer' is now the preferred term for the most commonly identified skin cancers basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), which were previously commonly categorised as non-melanoma skin cancers (NMSC). Keratinocyte cancer (KC) represents about 95% of malignant skin tumours. Lifestyle changes have led to increased exposure to the sun, which has, in turn, led to a significant increase of new cases of KC, with a worldwide annual incidence of between 3% and 8%. The successful use of preventive measures could mean a significant reduction in the resources used by health systems, compared with the high cost of the treatment of these conditions. At present, there is no information about the quality of the evidence for the use of these sun protection strategies with an assessment of their benefits and risks. OBJECTIVES: To assess the effects of sun protection strategies (i.e. sunscreen and barrier methods) for preventing keratinocyte cancer (that is, basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) of the skin) in the general population. SEARCH METHODS: We searched the following databases up to May 2016: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trial registries and the bibliographies of included studies for further references to relevant trials. SELECTION CRITERIA: We included randomised controlled clinical trials (RCTs) of preventive strategies for keratinocyte cancer, such as physical barriers and sunscreens, in the general population (children and adults), which may provide information about benefits and adverse events related to the use of solar protection measures. We did not include trials focused on educational strategies to prevent KC or preventive strategies in high-risk groups. Our prespecified primary outcomes were BCC or cSCC confirmed clinically or by histopathology at any follow-up and adverse events. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for eligibility using Early Review Organizing Software (EROS). Similarly, two review authors independently used predesigned data collection forms to extract information from the original study reports about the participants, methods of randomisation, blinding, comparisons of interest, number of participants originally randomised by arm, follow-up losses, and outcomes, and they assessed the risk of bias. We resolved any disagreement by consulting a third author and contacted trial investigators of identified trials to obtain additional information. We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included one RCT (factorial design) that randomised 1621 participants.This study compared the daily application of sunscreen compared with discretionary use of sunscreen, with or without beta-carotene administration, in the general population. The study was undertaken in Australia; 55.2% of participants had fair skin, and they were monitored for 4.5 years for new cases of BCC or cSCC assessed by histopathology. We found this study to be at low risk of bias for domains such as allocation, blinding, and incomplete outcome data. However, we found multiple unclear risks related to other biases, including an unclear assessment of possible interactions between the effects of the different interventions evaluated (that is, sunscreen and beta-carotene). We found no difference in terms of the number of participants developing BCC (n = 1621; risk ratio (RR) 1.03, 95% confidence interval (CI) 0.74 to 1.43) or cSCC (n = 1621; RR 0.88, 95% CI 0.50 to 1.54) when comparing daily application of sunscreen with discretionary use, even when analyses were restricted to groups without beta-carotene supplementation. This evidence was of low quality, which means that there is some certainty that future studies may alter our confidence in this evidence.We reported adverse events in a narrative way and included skin irritation or contact allergy.We identified no studies that evaluated other sun protection measures, such as the use of sun-protective clothing, sunglasses, or hats, or seeking the shade when outdoors. AUTHORS' CONCLUSIONS: In this review, we assessed the effect of solar protection in preventing the occurrence of new cases of keratinocyte cancer. We only found one study that was suitable for inclusion. This was a study of sunscreens, so we were unable to assess any other forms of sun protection. The study addressed our prespecified primary outcomes, but not most of our secondary outcomes. We were unable to demonstrate from the available evidence whether sunscreen was effective for the prevention of basal cell carcinoma (BCC) or cutaneous squamous cell carcinoma (cSCC).Our certainty in the evidence was low because there was a lack of histopathological confirmation of BCC or cSCC in a significant percentage of cases. Amongst other sources of bias, it was not clear whether the study authors had assessed any interaction effects between the sunscreen and beta-carotene interventions. We think that further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.

Spectral Neugebauer-based color halftone prediction model accounting for paper fluorescence.

We present a spectral model for predicting the fluorescent emission and the total reflectance of color halftones printed on optically brightened paper. By relying on extended Neugebauer models, the proposed model accounts for the attenuation by the ink halftones of both the incident exciting light in the UV wavelength range and the emerging fluorescent emission in the visible wavelength range. The total reflectance is predicted by adding the predicted fluorescent emission relative to the incident light and the pure reflectance predicted with an ink-spreading enhanced Yule-Nielsen modified Neugebauer reflectance prediction model. The predicted fluorescent emission spectrum as a function of the amounts of cyan, magenta, and yellow inks is very accurate. It can be useful to paper and ink manufacturers who would like to study in detail the contribution of the fluorescent brighteners and the attenuation of the fluorescent emission by ink halftones.

"Application of five different strategies to define a cohort of patients with knee osteoarthritis in a large primary care database".

BACKGROUND: Electronic health records (EHR) are frequently used for epidemiological research including drug utilisation studies in a defined population such as the population with knee osteoarthritis (KOA). We sought to describe the process of defining a cohort of patients with KOA from a large UK primary care database and estimate the annual incidence of diagnosed KOA between 2000 and 2015. METHOD: This was a retrospective study using data from the clinical practice research datalink (CPRD). CPRD is a large primary care longitudinal electronic medical records' database that contains anonymous records of patients from general practices across United Kingdom. Five different cohort definition strategies were applied including symptoms-based or diagnosis-based strategies or a combination of both. To validate results, the annual incidence of KOA was estimated and compared to published data. RESULTS: The study defined 898,690 patients when symptoms-based strategy was applied, 137,541 patients when diagnosis based and 83,294 when a combination of both strategies were applied. The final cohort was defined using a diagnosis-based strategy that avoided overestimation (with symptoms-based definition) or underestimation (with a combination of symptoms and diagnosis). The incidence of KOA ranged from 1.33 per 1000 CPRD registrants in 2000, 1.76 in 2008 and 1.45 patients in 2015. CONCLUSION: This study logically/sensibly defined a cohort of patients with diagnosed KOA through the application of several strategies. This was an essential step to avoid subsequent over or underestimation of the prevalence of drug utilisation and the associated adverse clinical outcomes within primary care patients with KAO.

Knee osteoarthritis patients assessed during walking for ankle inversion movement discrimination sensitivity.

Background: Knee osteoarthritis (KOA) is a common musculoskeletal condition that affects dynamic balance control and increases the risk of falling during walking. However, the mechanisms underlying this are still unclear. Diminished ankle proprioception during walking has been found to be related to fear of falling in older adults, with a gender difference in incidence of falling. This study aimed to determine 1) whether ankle inversion proprioceptive acuity during walking is impaired in patients with KOA; and 2) whether there is any difference between genders. Methods: Thirty-two patients with KOA (F:M = 17:15, Median age = 52.5, BMI = 22.3 ± 3.0) and 34 healthy controls without KOA (HC) (F:M = 17:17; median age = 49.0, BMI = 22.5 ± 2.7) were recruited. In patients with KOA, ankle inversion proprioceptive acuity was measured on the affected side using the ankle inversion discrimination apparatus for walking (AIDAW), whilst HC were assessed on a randomly selected side. Two-way (2*2) analysis of variance (ANOVA) was performed to determine the main effects and interaction between gender and KOA condition. Results: Two-way ANOVA showed a significant KOA main effect (F = 26.6, p < 0.001, ƞp 2 = 0.3) whereby AIDAW scores during walking for individuals with KOA were significantly lower than those without KOA (KOA vs. HC: 0.746 ± 0.057 vs. 0.807 ± 0.035). There was neither a gender main effect nor interaction (both p > 0.05). Conclusion: Individuals with KOA demonstrated lower ankle proprioception scores during walking compared to their healthy counterparts, with a similar level of impairment in ankle proprioceptive acuity between male and female patients. A low score may contribute to an increased risk of falling in the KOA population. The current findings suggest the need for global concern about lower limb proprioception in the clinical management of KOA.

Voluntary postural sway control and mobility in adults with low back pain.

Introduction: Low back pain (LBP) is associated with altered somatosensory perception, which is involved in both involuntary and voluntary control of posture. Currently, there is a lack of methods and tools for assessing somatosensory acuity in patients with LBP. The purpose of this study was (1) to assess the reliability of the sway discrimination apparatus (SwayDA) (2) to evaluate the differences in somatosensory acuity between patients with LBP and pain-free individuals, and (3) to examine relationships between somatosensory acuity, severity of LBP, and mobility in patients with LBP. Methods: Twenty participants (10 patients with LBP and 10 matched asymptomatic controls) were recruited in a test-retest reliability test. Another 56 participants were recruited for this study with 28 individuals presenting with LBP and a further twenty-eight being asymptomatic. The SwayDA was custom-built to measure somatosensory perception during voluntary anterior-posterior (SwayDA-AP), medial-lateral to the dominant side (SwayDA-ML-D), and non-dominant side (SwayDA-ML-ND) postural sway control. Participants also completed mobility tests, including 10 times and 1-min sit-to-stand tests (10-STS, 1 m-STS). The area under the receiver operating characteristic curve (AUC) was calculated to quantify somatosensory acuity in discriminating different voluntary postural sway extents. Results: The ICC (2.1) for the SwayDA-AP, SwayDA-ML-D, and SwayDA-ML-ND were 0.741, 0.717, and 0.805 with MDC95 0.071, 0.043, and 0.050. Patients with LBP demonstrated significantly lower SwayDA scores (tSwayDA-AP = -2.142, p = 0.037; tSwayDA-ML-D = -2.266, p = 0.027) than asymptomatic controls. The AUC values of the SwayDA-AP test were significantly correlated with ODI (rSwayDA-AP-ODI = -0.391, p = 0.039). Performances on the 1 m-STS and the 10-STS were significantly correlated with the AUC scores from all the SwayDA tests (-0.513 ≤ r ≤ 0.441, all p < 0.05). Discussion: The SwayDA tests evaluated showed acceptable reliability in assessing somatosensory acuity during voluntary postural sway. Somatosensory acuity was diminished in patients with LBP compared to asymptomatic controls. In patients with LBP, lower somatosensory acuity was associated with increased LBP-related disability. Future research could focus on investigating the factors contributing to the decreased somatosensory perception and mobility in individuals with LBP.

Functional Connectivity and Speech Entrainment Speech Entrainment Improves Connectivity Between Anterior and Posterior Cortical Speech Areas in Non-fluent Aphasia.

BACKGROUND: Speech entrainment (SE), the online mimicking of an audio-visual speech model, has been shown to increase speech fluency in individuals with non-fluent aphasia. One theory that may explain why SE improves speech output is that it synchronizes functional connectivity between anterior and posterior language regions to be more similar to that of neurotypical speakers. OBJECTIVES: The present study tested this by measuring functional connectivity between 2 regions shown to be necessary for speech production, and their right hemisphere homologues, in 24 persons with aphasia compared to 20 controls during both free (spontaneous) speech and SE. METHODS: Regional functional connectivity in participants with aphasia were normalized to the control data. Two analyses were then carried out: (1) normalized functional connectivity was compared between persons with aphasia and controls during free speech and SE and (2) stepwise linear models with leave-one-out cross-validation including normed functional connectivity during both tasks and proportion damage to the left hemisphere as independent variables were created for each language score. RESULTS: Left anterior-posterior functional connectivity and left posterior to right anterior functional connectivity were significantly more similar to connectivity of the control group during SE compared to free speech. Additionally, connectivity during free speech was more associated with language measures than connectivity during SE. CONCLUSIONS: Overall, these results suggest that SE promotes normalization of functional connectivity (i.e., return to patterns observed in neurotypical controls), which may explain why individuals with non-fluent aphasia produce more fluent speech during SE compared to spontaneous speech.

Association between mirtazapine use and serious self-harm in people with depression: an active comparator cohort study using UK electronic health records.

BACKGROUND: Studies report an increased risk of self-harm or suicide in people prescribed mirtazapine compared with other antidepressants. OBJECTIVES: To compare the risk of serious self-harm in people prescribed mirtazapine versus other antidepressants as second-line treatments. DESIGN AND SETTING: Cohort study using anonymised English primary care electronic health records, hospital admission data and mortality data with study window 1 January 2005 to 30 November 2018. PARTICIPANTS: 24 516 people diagnosed with depression, aged 18-99 years, initially prescribed a selective serotonin reuptake inhibitor (SSRI) and then prescribed mirtazapine, a different SSRI, amitriptyline or venlafaxine. MAIN OUTCOME MEASURES: Hospitalisation or death due to deliberate self-harm. Age-sex standardised rates were calculated and survival analyses were performed using inverse probability of treatment weighting to account for baseline covariates. RESULTS: Standardised rates of serious self-harm ranged from 3.8/1000 person-years (amitriptyline) to 14.1/1000 person-years (mirtazapine). After weighting, the risk of serious self-harm did not differ significantly between the mirtazapine group and the SSRI or venlafaxine groups (HRs (95% CI) 1.18 (0.84 to 1.65) and 0.85 (0.51 to 1.41) respectively). The risk was significantly higher in the mirtazapine than the amitriptyline group (3.04 (1.36 to 6.79)) but was attenuated after adjusting for dose. CONCLUSIONS: There was no evidence for a difference in risk between mirtazapine and SSRIs or venlafaxine after accounting for baseline characteristics. The higher risk in the mirtazapine versus the amitriptyline group might reflect residual confounding if amitriptyline is avoided in people considered at risk of self-harm. CLINICAL IMPLICATIONS: Addressing baseline risk factors and careful monitoring might improve outcomes for people at risk of serious self-harm.

Current use of analgesics and the risk of falls in people with knee osteoarthritis: A population-based cohort study using primary care and hospital records.

Objective: To examine the association between the current use of analgesics and the risk of falls in people with knee osteoarthritis (KOA). Methods: A retrospective cohort study using data from the UK Clinical Practice Research Datalink, with linkage to Hospital Episode Statistics data. People diagnosed with KOA in England between 2000 and 2014 were included. The studied analgesic classes were antidepressants, antiepileptic drugs (AEDs), opioids, non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol. Cox Proportional Hazards model was used to estimate the risk of fall with current use of analgesics within one year of KOA diagnosis, reported as Hazard Ratio (HR) with 95% Confidence Intervals (CI). Results: This study included 57,383 patients (mean age [SD] 67.0 [12.8] years, 59.3% were female); 44,010 (76.7%) were prescribed analgesics at least once within one year of KOA diagnosis. Within the first six months of KOA diagnosis, the reported HR (95%CI) were 1.46 (1.20, 1.78), 1.40 (0.91, 2.16), 2.40 (2.01, 2.85), 1.72 (1.43, 2.07), 1.98 (1.68, 2.33), while between 6 and 12 months after KOA diagnosis, the HR (95%CI) were 2.68 (2.14, 3.36), 2.22 (1.70, 2.91), 1.96 (1.70, 2.26), 1.47 (1.21, 1.78), 1.92 (1.63, 2.26) for antidepressants, AEDs, opioids, NSAIDs and paracetamol, respectively and adjusted for important potential confounders. Conclusion: The current use of analgesics was associated with an increased risk of falls within one year of KOA diagnosis. These findings identify people with KOA who use analgesics as a priority for fall prevention programs/interventions, in an effort to optimise safety of analgesics in this population.

Estimating crop parameters using Sentinel-1 and 2 datasets and geospatial field data.

Crop monitoring is essential for ensuring food security in a global context of population growth and climate change. Satellite images are commonly used to estimate crop parameters over large areas, and the freely available Synthetic Aperture Radar (SAR) Sentinel-1 (S-1) and optical Sentinel-2 (S-2) images are relevant for that purpose combining high temporal resolution and high spatial resolution. For this data article, field surveys were conducted from January to July 2017 in France to sample wheat and rapeseed crop parameters during the entire crops cycle. Phenological stages were identified in 83 wheat fields and 32 rapeseed fields in Brittany and Picardy regions. Moreover, Leaf Area Index (LAI), wet biomass, dry biomass and water content were sampled in three wheat fields and three rapeseed fields in Brittany. We assigned to each field sample 10 spectral bands and 12 vegetation indices from S-2 images and two backscattering coefficients, one backscattering ratio and four polarimetric indicators from S-1 images. This dataset can be used for crop monitoring in other regions, as well as for modelling development.

Analyzing halftone dot blurring by extended spectral prediction models.

Spectral prediction models for halftone prints generally assume homogeneously thick and sharply edged ink dots, i.e., bilevel halftones. In real prints, the ink thickness often decreases at the boundaries of the ink dots, thereby forming continuous-level halftones. The present study aims at verifying to what extent the classical Clapper-Yule and Yule-Nielsen models are able to predict the reflectance of single-ink continuous-level halftone prints. First we model the reflectance of continuous-level halftones by developing variable thickness extensions of both the Clapper-Yule and the Yule-Nielsen spectral prediction models. We consider continuous halftones whose thickness profiles are obtained by Gaussian filtering of the bilevel halftone image. Then we predict the reflectance spectra defined by the continuous-level models by fitting the bilevel models' effective ink surface coverages. Since dot blurring tends to increase the absorption of light by the ink, the effective ink surface coverage is larger than the nominal one, i.e., dot blurring induces its own contribution to dot gain. Dot blurring can also be accurately modeled by an increased n-value of the classical Yule-Nielsen model.

Changes in soil cadmium concentrations with time following cessation of phosphorus fertilizer inputs.

Cadmium (Cd) can accumulate in soil from the application of phosphorus fertilizer. However, there is little information on what happens to soil Cd concentrations when Cd inputs stop. This study used soil and pasture samples collected from a long-term field trial to measure changes in Cd concentrations in soil for 22 yr after Cd inputs from fertilizer had stopped and assessed whether the application of nitrogen (N) (50 kg ha-1  yr-1 ) could increase plant uptake of Cd and reduce soil Cd concentrations. It was found that there was no significant change in total or labile soil Cd (1 M CaCl2 extractable) concentrations after Cd inputs stopped. The application of N did not significantly (P < .05) increase dry matter yield or increase Cd solubility. As a result, N did not enhance plant uptake of Cd. A mass balance that included Cd loss via plant uptake and Cd leaching confirmed they were insufficient to result in a detectable decrease in soil Cd concentration over the 22-yr interval of the trial. It appears that even an acid soil with low amounts of carbon (2.67%), iron/aluminum oxides, and clay can still strongly retain Cd, preventing Cd depletion from the soil, despite stopping Cd inputs and trying to enhance plant uptake of Cd from the application of N fertilizer.